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Objectives: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next‐generation sequencing (NGS) and clinical‐exome‐based copy number variant (CNV) analysis in patients with CHA. Methods: One hundred and forty‐three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole‐exome sequencing in nine patients. Exome‐based CNV calling was incorporated into the traditional single‐nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long‐range polymerase chain reaction. Results: Molecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR. Conclusions: In this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success. [ABSTRACT FROM AUTHOR]

The article discusses two cases of childhood interstitial lung disease (chILD) with undefined causes, potentially related to telomere variants. Telomeres are nucleoprotein complexes at the ends of chromosomes, and telomere-related variants have been linked to interstitial lung disease in adults. The patients in the cases presented tested positive for telomere-related variants, highlighting the importance of evaluating telomere length in children with chILD. The study emphasizes the need for genetic analysis in pediatric patients with chronic ILD to identify new genetic entities and underscores the importance of ongoing monitoring for potential long-term effects of telomere variants in these patients. [Extracted from the article]

Basal cell carcinoma (BCC) is a rare secondary malignancy which may occur more often in children with acute lymphoblastic leukemia (ALL) who have previously received radiation therapy compared to to those who received no radiation. [ABSTRACT FROM AUTHOR]

CDA are a group of inherited, rare diseases that are characterized by dyserythropoiesis and ineffective erythropoiesis associated with transfusion dependency in approximately 10% of cases. For these latter patients, the only curative treatment is HSCT. There are very limited data on HSCT experience in this rare disease. Herein, we report a five-yr six-month-old girl with compound heterozygous mutations in SEC23B gene, who was diagnosed to have CDA type II and underwent successful HSCT from her matched sibling donor. [ABSTRACT FROM AUTHOR]

Objectives: An observational study was conducted to explore postmarketing safety and efficacy of Deferasirox (DFX) in comparison with conventional Desferrioxamine (DFO) in chelation-naïve children with transfusional iron overload. Methods: Transfusion-dependent children (aged ≤5 yr) who had serum ferritin above 1000 μg/L and had been prescribed either first-line DFX or DFO for at least 12 months to maintain serum ferritin between 500 and 1000 μg/L were included. Initial DFX dose was 20 mg/kg/d for 7 d a week, and DFO dose was 25-35 mg/kg/d subcutaneously, given for 5 d a week. Dose adjustments were based on serum ferritin changes and safety markers. The primary efficacy endpoint was change in serum ferritin from baseline. The effect of transfusional iron loading rate (ILR) and different doses of chelators on serum ferritin was also assessed. Results: A total of 111 patients were observed for a median of 2.29 yr on DFX ( n = 71) and 2.75 yr on DFO ( n = 40). Absolute change in serum ferritin from baseline to the last available observation was not significant with DFX (91 μg/L, P = 0.5) but significantly higher with DFO (385 μg/L, P < 0.005). ILR and DFX doses had a major impact on serum ferritin changes in DFX cohort. The height- and weight-standard deviation scores did not differ significantly in both cohorts during the study. Fluctuations in liver enzymes and non-progressive increase in serum creatinine were the most common adverse events (DFX; 9.8%, 18.0% and DFO; 5.0%, 7.5%, respectively). Conclusion: DFX is well tolerable and at least as effective as DFO to maintain safe serum ferritin levels and normal growth progression in chelation-naïve children. [ABSTRACT FROM AUTHOR]

The data of allogeneic HSCT in nine children with acquired AA between June 1998 and July 2006 were analyzed retrospectively. The median duration of time to neutrophil and platelet engraftment was 18 and 25 days, respectively. None of the patients had primary graft failure. Two (22.2%) patients developed acute GVHD and of these, one (11.1%) was Grade 1, and the other (11.1%) was Grade 3. Although the study group was composed of higher risk patients, including six of nine resistant to previous immunosuppressive treatment, eight had multiple not irradiated or filtered transfusion histories and one of the cases was only 5/6 HLA-compatible with his donor, the five-yr overall and EFS was 100%, and all recipients are alive without any graft failure. This may be attributed to the dose adjusted use of ATG according to individual transfusion history and gradual tapering of CsA and cessation at least nine months after allogeneic HSCT. [ABSTRACT FROM AUTHOR]

Recently, there are emerging reports on the beneficial effect of imatinib mesylate for pediatric CML patients; however, the general recommendation is that high-risk CML patients with a human leukocyte antigen-identical donor should be transplanted within the first 12 months after diagnosis. Herein, the data of 16 allogeneic HSCT in 14 children with CML were analyzed retrospectively. In the present study, three-yr EFS was 54.1 ± 10.8% and three-yr OS was found as 80.7 ± 12.5%. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to evaluate the rate of hepatitis B and C virus infection and emphasize the importance of hepatitis B virus (HBV) vaccination in leukemic children. Methods: One hundred and sixty children who were treated for acute lymphoblastic leukemia (ALL) at Hacettepe University Faculty of Medicine, Pediatric Hematology Unit were included in the study. They were 71 (44.4%) girls and 89 (55.6%) boys with a mean age of 6.45 ± 3.87 years. Results: Of these 160 children, 22 (13.8%) were anti-HBs-positive and 138 (86.2%) were anti-HBs-negative at the diagnosis of ALL. Among the 138 anti-HBs-negative children, 67 (41.9%) were vaccinated for HBV during maintenance chemotherapy, and 71 (44.3%) could not be vaccinated. Two (2.9%) vaccinated and 22 (30.9%) unvaccinated children developed HBV infection during the follow-up period ( P < 0.001). Among 160 children treated for ALL, 24 (15.0%) had HBV, three (1.9%) had hepatitis C virus (HCV) infections, and 29 (18.1%) had toxic hepatitis. The majority of patients with HBV or HCV infections had high risk (HR) protocol, whereas most of the patients with toxic hepatitis had low risk (LR) protocol, especially St Jude Total XIII LR protocol. Conclusion: Viral hepatitis and toxic hepatitis were observed more commonly in the HR and LR group, respectively, of ALL patients. This could be explained by intensive chemotherapy and more heavy blood product administration in the HR group and the chemotherapeutic agents of methotrexate and 6-mercaptopurine, basic drugs used in the LR group. In respect to protection from these complications, periodical liver function tests, serological tests for HBV and HCV, and vaccination for HBV should be performed for all children with ALL. [ABSTRACT FROM AUTHOR]

Severe amitriptyline toxicity may cause coma, hypotension, convulsions, supraventricular and ventricular arrhythmias, metabolic/respiratory acidosis and cardiac arrest. Management with gastric lavage, activated charcoal, alkalinization with sodium bicarbonate and supportive care with mechanical ventilation, antiarrhythmics and anticonvulsants if required, is the common approach. Herein, we report successful treatment of severe amitriptyline poisoning in three cases by plasma exchange in addition to the above supportive measures. Plasma exchange may have a beneficial role in lethal doses of amitriptyline ingestion because of the high plasma protein binding property of amitriptyline. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome characterized by pancytopenia, increased susceptibility to malignancies, and a spectrum of congenital anomalies. Here, we report on eight affected individuals from six unrelated families with a large Alu-mediated intragenic deletion encompassing exons 6-31 in the FANCA gene, identified as a founder mutation in the Turkish population through haplotype analysis. This deletion, mediated by Alu repeat sequences, underscores the role of repetitive elements in FA pathogenesis. Clinical data revealed variable phenotypic presentations among affected individuals, highlighting the challenge of establishing genotype-phenotype correlations even in the presence of identical FANCA pathogenic variants. We carried out an easy and effective PCR-based diagnostic test for detecting this mutation, enabling precise diagnosis and genetic counseling for affected individuals and their families. This study provides valuable insights into the molecular mechanisms underlying FA pathogenesis and offers a practical approach for genetic diagnosis in affected individuals, particularly those of Turkish descent., (© 2024 Wiley Periodicals LLC.)